Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes

Dipta, Priya; Sarsenbayeva, Assel; Shmuel, Miriam; Forno, Francesca; Eriksson, Jan W.; Pereira, Maria J.; Abalo, Xesús M.; Wabitsch, Martin; Thaysen‐Andersen, Morten; Tirosh, Boaz

doi:10.1016/j.cpnec.2021.100073

Cited by 5 publications

(2 citation statements)

References 69 publications

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“…Up-regulated genes associated with M1 polarization include CCR7 , CD80 , CD86 , CXCL10 , CXCL11 , IL15RA , IL1B , MET , and STAT1 . [ 22 , 33 , 34 , 35 , 36 ] Up-regulated genes associated with M2 polarization include CD163 , CD209 , CLEC7A , CXCL12 , EGR2 , HIF1A , HMOX1 , IL10 , MMP2 , PPAR , SPP1 , and TGFB1 . [ 22 , 33 , 34 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages

Scobie

Abood

Rice

2023

IJMS

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A common theme in glioma disease progression is robust infiltration of immune cells within the tumor microenvironment, resulting in a state of chronic inflammation. This disease state is characterized by an abundance of CD68+ microglia and CD163+ bone marrow-derived macrophages with the greater the percentage of CD163+ cells, the poorer the prognosis. These macrophages are “cold,” in that their phenotype is of an alternatively activated state (M0-M2-like) supporting tumor growth rather than being engaged with classically activated, pro-inflammatory, and anti-tumor activities, referred to as “hot”, or M1-like. Herein, we have developed an in vitro approach that uses two human glioma cell lines, T98G and LN-18, which exhibit a variety of differing mutations and characteristics, to demonstrate their disparate effects on differentiated THP-1 macrophages. We first developed an approach to differentiating THP-1 monocytes to macrophages with mixed transcriptomic phenotypes we regard as M0-like macrophages. We then found that supernatants from the two different glioma cell lines induced different gene expression profiles in THP-1 macrophages, suggesting that from patient to patient, gliomas may be considered as different diseases. This study suggests that in addition to standard glioma treatment modalities, transcriptome profiling of the effects of cultured glioma cells on a standard THP-1 macrophage in vitro model may lead to future druggable targets that aim to reprogram tumor-associated macrophages towards an anti-tumor phenotype.

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Section: Resultsmentioning

confidence: 99%

Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages

Scobie

Abood

Rice

2023

IJMS

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“…For macrophages differentiation, 10 ng/mL granulocyte-macrophage colony-stimulating factor (GM-CSF; Miltenyi Biotec, #130093865) was added to isolated monocytes and cells were incubated for 10 days in RPMI 1640 culture medium (Gibco #11875093) supplemented with 10% (v/v) heat-inactivated FBS (Gibco), 1% sodium pyruvate, 1% penicillin/streptomycin, 1% (all w/v) non-essential amino acid (Thermo). Polarization into anti-inflammatory macrophages was performed using 20 ng/mL IL-4 and 20 ng/ml IL-13 (Miltenyi Biotec) as described 74 and confirmed with CD206 marker expression through flow cytometry.…”

Section: Isolation Of Human Monocytes Macrophage Differentiation and ...mentioning

confidence: 99%

Tumor- and immune-derivedN-acetyl-β-D-hexosaminidase drive colorectal cancer and stratify patient risk

Kawahara,

Kautto,

Bansal

et al. 2024

Preprint

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SummaryNon-invasive prognostic markers are needed to improve survival of colorectal cancer (CRC) patients. Towards this goal, we applied integrative systems glycobiology approaches to tumor tissues and PBMCs from CRC patients and matching controls as well as to a CRC patient-derived cell line. Firstly, quantitative glycomics and glycoproteomics revealed that non-canonical paucimannosidic proteins from monocytic and cancer cell origins are prominent signatures in CRC tumor tissues, and that their expression associates with CRC progression. Guided by these associations, we then showed thatN-acetyl-β-D-hexosaminidase (Hex) facilitates paucimannosidic protein biosynthesis in CRC cells and is intimately involved in processes underpinning CRC metastasis (adhesion, migration, invasion, proliferation). Finally, Hex activity was found to be elevated in PBMCs and plasma from patients with advanced CRC relative to matching controls while plasma Hex activity correlated strongly with CRC patient survival. Our study opens avenues for better prognostication, disease risk stratification and therapeutic interventions in CRC.Highlights•Non-canonical truncated glycans of immune and cancer origins dominate in CRC tumors•N-acetyl-β-D-hexosaminidase, a truncating glycoenzyme, drives tumorigenesis in CRC•Activity of plasmaN-acetyl-β-D-hexosaminidase stratifies risk in CRC patients

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Excess glucocorticoid exposure contributes to adipose tissue fibrosis which involves macrophage interaction with adipose precursor cells

Sarsenbayeva

Pereira

Jui

et al. 2022

Biochemical Pharmacology

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Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes

Cited by 5 publications

References 69 publications

Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages

Differential Transcriptome Responses in Human THP-1 Macrophages Following Exposure to T98G and LN-18 Human Glioblastoma Secretions: A Simplified Bioinformatics Approach to Understanding Patient-Glioma-Specific Effects on Tumor-Associated Macrophages

Tumor- and immune-derivedN-acetyl-β-D-hexosaminidase drive colorectal cancer and stratify patient risk

Excess glucocorticoid exposure contributes to adipose tissue fibrosis which involves macrophage interaction with adipose precursor cells

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